Approximately 10% of the population become hypersensitized (allergic) upon exposure to antigens from a variety of environmental sources. Those antigens that induce immediate and/or delayed types of hypersensitivity are known as allergens (King, T. P., (1976) Adv. Immunol., 23:77-105). These include products of grasses, trees, weeds, animal dander, insects, food, drugs, and chemicals. Genetic predisposition of an individual is believed to play a role in the development of intermediate allergic responses (Young, R. P. et al., (1990) Clin. Sci., 79:19) such as atopy and anaphylaxis whose symptoms include hay fever, asthma, and hives.
The antibodies involved in atopic allergy belong primarily to the IgE class of immunoglobins. IgE binds to basophils, mast cells and dendritic cells via a specific, high-affinity receptor FcεRI (Kinet, J. P., (1990) Curr. Opin. Immunol., 2:499-505). Upon combination of an allergen acting as a ligand with its cognate receptor IgE, FceRI bound to the IgE may be cross-linked on the cell surface, resulting in physiological manifestations of the IgE-allergen interaction. These physiological effects include the release of, among other substances, histamine, serotonin, heparin, chemotactic factor(s) for eosinophilic leukocytes and/or leukotrienes C4, D4, and E4, which cause prolonged constriction of bronchial smooth muscle cells (Hood, L. E. et al., Immunology (2nd ed.), The Benjamin/Cumming Publishing Co., Inc. (1984)). Hence, the ultimate consequence of the interaction of an allergen with IgE is allergic symptoms triggered by the release of the aforementioned mediators. Such symptoms may be systemic or local in nature, depending on the route of entry of the antigen and the pattern of deposition of IgE on mast cells or basophils. Local manifestations generally occur on epithelial surfaces at the site of entry of the allergen. Systemic effects can induce anaphylaxis (anaphylactic shock) which results from IgE-basophil response to circulating (intravascular) antigen.
Studies with purified allergens have shown that about 80% of patients allergic to the mite Dermatophagoides pteronyssinus produce IgE reactive to Der p I and Der p II (Chapman M. D. et al., J. Immunol. (1980) 125:587-92; Lind P., J. Allergy Clin. Immunol. (1985) 76:753-61; Van der Zee J. S. et al., J. Allergy Clin. Immunol. (1988) 8:884-95). For about half of the patients, these specificities constitute 50% of the IgE antimite antibody. The allergen Der p III, recently identified as trypsin, (Stewart G. A. et al, Immunology (1992) 75:29-35) reacts with a similar or higher frequency (Stewart G. A. et al, supra; Ford S. A. et al., Clin. Exp. Allergy (1989) 20:27-31). However, in the only quantitative study performed to date, the investigators reported the level of IgE binding to be considerably less than Der p I. Electrophoretic techniques (Ford S. A. et al, supra; Bengtsson A. et al, Int. Arch. Allergy Appl. Immunol. (1986) 80:383-90; Lind P. et al, Scand. J. Immunol. (1983) 17:263-73; Tovey E. R. et al, J. Allergy Clin. Immunol. (1987) 79:93-102) have shown that most sera recognize other allergens. For example, in the study of Ford et al. (supra) Western blotting showed 8 sera reacting with 1-2 bands, 6 with 3-6 and 3 with a greater number including one with at least 13. In another study, Baldo et al. (Adv. Bioscience (1989) 4:13-31) report the finding of components at Mr 30, 26, 25K reacting with 50% of sera. To determine the importance of particular specificities in the allergic reactions, purified allergens would be required for quantitative IgE binding tests and to examine the frequency and lymphokine profile for T cell reactivity.
Treatment of patients with sensitivity to house dust mites by administration of increasing doses of house dust extracts has the drawbacks of potential anaphylaxis during treatment and the possible necessity of continuing therapy over a period of several years to build up sufficient tolerance that results in significant diminution of clinical symptoms. A therapeutic composition and method of therapy which avoids these problems would be beneficial.